Ming-Jer Tsai, Ph.D.
C.C. Bell Professor, Department of Molecular and Cellular Biology
Ph.D., University of California, Davis
Postdoctoral, The University of Texas M.D. Anderson Cancer Center
Research Interests:
We are interested in understanding the role of transcription factors in gene regulation, development and diseases. Our research has been concentrated in the following three areas:
1. BETA2/NeuroD in pancreatic Islet and neuronal development: The insulin gene is regulated in a tissue and developmental-specific manner. In our laboratory, we have isolated a tissue-specific transcription factor BETA2 that can regulate its transcription. Its role in insulin gene activity and islet cell fate determination are carried out by gene knockout experiment. Results indicate that BETA2 is essential for proper morphogenesis of pancreatic islets and cell fate determination of several enteroendocrine cells. In addition, we also found that the proper differentiation of several neuronal cell types such as granule cells of the hippocampus and cerebellum, photoreceptor cells of retina, as well as the ganglions of the number VIII nerve are compromised. These defects result in behavior abnormalities such as epilepsy, hyperactivity, imbalance and deafness. Currently, we are analyzing the target genes that are responsible for these defects and modifying mechanism of these defects. In addition, using Ngn3, a bHLH transcription factor, as a marker and molecular genetic approaches to mark Ngn3 cells, we have isolated islet progenitor/stem cells. These cells will be characterized for future treatment of diabetes using in vitro produced islets from these progenitor/stem cells.
2. Molecular developmental biology of COUP-Transcription factors: COUP-TFs are orphan members of the steroid/thyroid receptor superfamily. Using a molecular approach in collaboration with Dr. Sophia Tsai's laboratory, we have found that COUP-TFs are silencers and able to negatively regulate other receptors such as RAR, RXR, TR, VDR and PPAR activities. These results suggest that they play an important role in cellular development and differentiation. We are using cellular, molecular and genetic approaches to determine the precise role(s) of these transcription factors in mouse development. Results indicated that COUP-TFI is important in neurodevelopment, axonal guidance, brain regionalization and bone morphogenesis and COUP-TFII is important for angiogenesis, heart development, adipogenesis and organogenesis. Currently, we are trying to dissect the underlying mechanism of these defects.
3. Role of nuclear receptor coactivators and corepressors in prostate cancer: It has been shown that androgen and its receptor play an important role in the formation and progression of prostate tumor. Activation of target genes by androgen receptor, however, requires the participation of coactivators and corepressors. Many cofactors have been identified to interact with and activate androgen receptor activity. In our laboratory, we are interesting in determining whether any of these cofactors has a role in prostate tumors. Using in situ hybridization, we have identified SRC-3 to be over-expressed in 47% of prostate tumor samples. Our goal is to dissect the role of SRC-3 in cell growth and formation of prostate tumor using transgenic mice as a model.
Selected Publications:
Li, L., Xie, X., Qin, J., Jeha, G., Saha, P.K., Yan, J., Haueter, C.M., Chan, L., Tsai, S.Y. and Tsai, M.-J. (2009) The Nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis and energy metabolism. Cell Metabolism 9: 77-87.
Kim, B.J., Takamoto, N., Yan, J., Tsai, S.Y. and Tsai, M.-J. (2009) Chicken Ovalbumin Upstream Promoter - Transcription Factor II (COUP-TFII)regulates growth and patterning of postnatal mouse cerebellum. Development Biology 326: 378-391.
Yan, J., Erdem, H., Ayala, G., Ittmann, M., Yu-Lee, L.Y., Tsai, S.Y. and Tsai, M.-J. (2008). SRC-3/AIB1 promotes cell motility and invasiveness through focal adhesion turnover and matrix metalloproteinase expression. Cancer Research 68: 5460-5468.
Kurihara K, Lee D-K, Petit FG, Jeong J, Lee K, Lydon JP, DeMayo FJ, Tsai M-J and Tsai SY. (2007). COUP-TFII Mediates Progesterone Regulation of Uterine Implantation by Controlling ER Activity. PLoS Genetics 3:e102, 1053-1064.
Yan J, Yu C-T, Ozen M, Ittmann M, Tsai SY and Tsai M-J. (2006). Steroid receptor coactivator-3 and AP-1 coordinately regulates the transcription of components of the IGF/AKT signaling pathway. Cancer Research 66:11039-11046.
You LR, Takamoto N, Tanaka T, Kodama T, DeMayo FJ, Tsai SY and Tsai M-J. (2005). Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc. Natl. Acad. Sci. USA 102:16351-16356.
You L-R, Lin F-J, Lee CT, DeMayo FJ, Tsai M-J and Tsai SY. (2005). Suppression of Notch signaling by the nuclear receptor COUP-TFII is required for the establishment of vein identity. Nature 435:98-104.
Chu K and Tsai M-J. (2005). Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose mediated insulin secretion. Diabetes 54:1064-1073.
Bramblett DE, Pennesi ME, Wu SM and Tsai M-J. (2004). The transcription factor Bhlhb4 is required for rod bipolar cell maturation. Neuron 43:779-793.
Zhou C, Tsai SY and Tsai M-J. (2001). COUP-TFI: an intrinsic factor for early regionalization of the neocortex. Genes & Development 15:2054-2059.
Liu M, Pereira FA, Price SD, Chu M, Shope C, Himes D, Eatock RA, Brownell W, Lysakowski A and Tsai M-J. (2000). Essential role of BETA2/NeuroD in development of the vestibular and auditory systems. Genes and Development 14:2839-2854.
Zhou C, Qiu Y, Pereira FA, Crair MC, Tsai SY and Tsai M-J. (1999). The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron 24:847-859.
For more publications, see listing on PubMed.
Contact Information:
Ming-Jer Tsai, Ph.D.
Department of Molecular and Cellular Biology
Baylor College of Medicine
One Baylor Plaza, Room M-734
Houston, TX 77030
(713) 798-6253
Fax: (713) 798-8227
E-mail: mtsai@bcm.edu
Updated: 11/09